A great number of ancient marine invertebrate species in the Phyla Bryozoa, Mollusca and Porifera were well established in the earth's oceans over one billion years ago. Certainly such organisms had explored trillions of biosynthetic reactions in their evolutionary chemistry to reach present levels of cellular organization, regulation and defense. Marine sponges have changed minimally in physical appearance for nearly 500 million years, suggesting a very effective chemical evolution in response to changing environmental conditions for at least that time period. Some recognition of the potential for utilizing biologically potent marine animal constituents was recorded in Egypt about 2,700 BC, and by 200 BC sea hare extracts were being used in Greece for medicinal purposes. Such considerations, combined with the general observation that marine organisms (especially invertebrates and sharks) rarely develop cancer, led to the first systematic investigation of marine animal and plant anticancer constituents.
By 1968 ample evidence had been obtained, based on the U.S. National Cancer Institute's key experimental cancer systems, that certain marine organisms would provide new and structurally novel antineoplastic and/or cytotoxic agents. Analogous considerations suggested that marine organisms could also provide effective new drugs for other severe medical challenges, such as viral types, that would have eluded discovery by contemporary techniques of medicinal chemistry. Fortunately these expectations have been realized in the intervening period. Illustrative of these successes are discoveries of the bryostatins, dolastatins, and cephalostatins where five members of these series of remarkable anticancer drug candidates are either now in human clinical trial or preclinical development.
As is well known to those presently engaged in medical research, the time between the isolation of a new compound, and its introduction to the market place takes at least several years in the best case, and can take several decades, when an entity to finance the tortuous regulatory trail is slow to appear.
Consequently, industry, in association with the government, has devised a number of qualifying tests which serve two purposes. One aim is to eliminate those substances whose results in the qualifiers unequivocally demonstrate that the further expenditure of funds thereon would be economically counterproductive. The second, and primary aim, is to identify those substances which demonstrate a high likelihood of success and therefore warrant the requisite further investment necessary to obtain the data which is required to meet the various regulatory requirements imposed by those governments which regulate the market place into which such substances will enter.
The present cost of obtaining such data approaches Ten Million Dollars($10,000,000 U.S.) per compound. Economics dictate that such an investment be made only when there is a reasonable opportunity for it to be recovered. This opportunity can only be provided through patent protection. Absent such protection, there will be no such investment, and the advances in such life saving drugs will stop.
Only two hundred years ago, many diseases ravaged humankind. Many of these diseases have been controlled or eradicated. In the development of the means to treat or control these diseases, work with the appropriate common experimental animals was of critical importance. With the various types of cancers, and with the HIV virus, such work is presently ongoing. The research for the treatment of various types of cancer is coordinated by the National Cancer Institute (NCI).NCI, as a government entity, has been charged with assisting anti-cancer research. To establish whether a substance has anti cancer activity, NCI has established a protocol. This protocol, which involves testing a substance against a cell line panel containing 60 human tumor cell lines, has been verified, and is accepted in scientific circles. This protocol, and the established statistical means of evaluating the results obtained therefrom have been amply described in the literature. See e.g. Principles & Practice of Oncology PPO Updates, Volume 3, Number 10, October 1989, by Michael R. Boyd, M.D., Ph.D., for a description of the protocol. The statistical analysis is explained in "Display and Analysis of Patterns of Differential Activity of Drugs Against Human Tumor Cell Lines: Development of Mean Graph and COMPARE Algorithm" Journal of the National Cancer Institute Reports Vol. 81, No. 14, Pg. 1088, Jul. 14, 1989, by K. D. Paull et al. Both articles are incorporated herein by this reference as if fully set forth.
The Constitution of the United States (Art.1, Sec.8), authorizes Congress to establish the United States Patent and Trademark Office(USPTO) to promote scientific advancement. This obligation can only be fully met when the USPTO accepts current medical and scientific realities in the area of medical research.
The Framers of the Constitution meant for the Patent system to advance, not hamstring, scientific advancement. Cells are alive. The impairment of human tumor cell growth is utility. The sole right obtained by the grant of Letters Patent is that of preventing others from exploiting the subject matter of the patent. The recognition of cell line testing as evidence of antineoplastic activity and hence utility can only aid research in the United States, and will prevent the citizens of the United States from being held hostage by foreign governments or foreign corporations, which could otherwise procede with such projects in a less stringent environment, especially if such research is no longer viable in the United States.
Numerous compounds have been discovered which demonstrate significant antineoplastic activity. As discussed above, many of these compounds have been extracted, albeit with great difficulty, from living creatures such as the sponge or the sea hare. However, once the isolation and testing of such compounds has progressed, a practical problem exists, namely, how to obtain a significant quantity of the compound.
Unlike cinchona bark which was collected to produce quinine, and has an excellent yield, the collection and processing of these compounds in their natural occurring state ranges from the grossly impractical to the utterly impossible. Even ignoring potential ecological effects, the population of such creatures is clearly insufficient.
Accordingly, the elucidation of the absolute structure of such an antineoplastic compound is essential. After the absolute structure has been determined, then means of synthesis must be discovered. Additionally, research is essential to the determination of whether any portion of the naturally occurring compound is irrelevant to the desired properties thereof, which aids in determining the simplest structure which needs to be synthesized in order to obtain the perceived antineoplastic properties.